Ultra-Low Amplitude Cepheids in the Large Magellanic Cloud

The MACHO variables of LMC Field 77 that lie in the vicinity of the Cepheid instability strip are reexamined. Among the 144 variables that we identify as Cepheids we find 14 that have Fourier amplitudes <0.05 mag in the MACHO red band, of which 7 have an amplitude <0.006 mag : we dub the latter group of stars ultra-low amplitude (ULA) Cepheids. The variability of these objects is verified by a comparison of the MACHO red with the MACHO blue lightcurves and with those of the corresponding OGLE LMC stars. The occurrence of ULA Cepheids is in agreement with theory. We have also discovered 2 low amplitude variables whose periods are about a factor of 5--6 smaller than those of F Cepheids of equal apparent magnitude. We suggest that these objects are Cepheids undergoing pulsations in a surface mode and that they belong to a novel class of Strange Cepheids (or Surface Mode Cepheids) whose existence was predicted by Buchler et al. (1997).Comment: 4 pages, 5 figures, slightly revised, to appear in ApJ Letter

Major combined electrolyte deficiency during therapy with low-dose Cisplatin, 5-Fluorouracil and Interferon alpha: report on several cases and review of the literature [ISRCTN62866759]

BACKGROUND: Low-dose Cisplatin and Interferon alpha treatment of solid tumors rarely has been associated with severe hypocalcaemia. To the authors knowledge the phenomenon has not been reported previously in patients with pancreatic carcinoma. CASE PRESENTATION: A patient with resected adenocarcinoma of the pancreas was treated with adjuvant radio-chemo-immunotherapy using a combination of low-dose Cisplatin, 5-Fluorouracil and Interferon alpha together with external beam radiation. Severe hypocalcaemia without signs of acute renal failure or electrolyte disturbance occurred within 2 days at the 4th week of treatment and required intensive care treatment. CONCLUSION: Combination of biological and cytotoxic therapies may increase the incidence of severe hypocalcaemia in pancreatic cancer. Oncologists should remain attentive of this problem as more highly active regimes become available

Diagnostic strategy and timing of intervention in infected necrotizing pancreatitis: an international expert survey and case vignette study

AbstractBackgroundThe optimal diagnostic strategy and timing of intervention in infected necrotizing pancreatitis is subject to debate. We performed a survey on these topics amongst a group of international expert pancreatologists.MethodsAn online survey including case vignettes was sent to 118 international pancreatologists. We evaluated the use and timing of fine needle aspiration (FNA), antibiotics, catheter drainage and (minimally invasive) necrosectomy.ResultsThe response rate was 74% (N = 87). None of the respondents use FNA routinely, 85% selectively and 15% never. Most respondents (87%) use a step-up approach in patients with infected necrosis. Walled-off necrosis (WON) is considered a prerequisite for endoscopic drainage and percutaneous drainage by 66% and 12%, respectively. After diagnosing infected necrosis, 55% routinely postpone invasive interventions, whereas 45% proceed immediately to intervention. Lack of consensus about timing of intervention was apparent on day 14 with proven infected necrosis (58% intervention vs. 42% non-invasive) as well as on day 20 with only clinically suspected infected necrosis (59% intervention vs. 41% non-invasive).DiscussionThe step-up approach is the preferred treatment strategy in infected necrotizing pancreatitis amongst expert pancreatologists. There is no uniformity regarding the use of FNA and timing of intervention in the first 2–3 weeks of infected necrotizing pancreatitis

Strategies for protein synthetic biology

Proteins are the most versatile among the various biological building blocks and a mature field of protein engineering has lead to many industrial and biomedical applications. But the strength of proteins—their versatility, dynamics and interactions—also complicates and hinders systems engineering. Therefore, the design of more sophisticated, multi-component protein systems appears to lag behind, in particular, when compared to the engineering of gene regulatory networks. Yet, synthetic biologists have started to tinker with the information flow through natural signaling networks or integrated protein switches. A successful strategy common to most of these experiments is their focus on modular interactions between protein domains or domains and peptide motifs. Such modular interaction swapping has rewired signaling in yeast, put mammalian cell morphology under the control of light, or increased the flux through a synthetic metabolic pathway. Based on this experience, we outline an engineering framework for the connection of reusable protein interaction devices into self-sufficient circuits. Such a framework should help to ‘refacture’ protein complexity into well-defined exchangeable devices for predictive engineering. We review the foundations and initial success stories of protein synthetic biology and discuss the challenges and promises on the way from protein- to protein systems design

Diagnosis and treatment of pancreatic duct disruption or disconnection: an international expert survey and case vignette study

Background: Pancreatic duct disruption or disconnection is a potentially severe complication of necrotizing pancreatitis. With no existing treatment guidelines, it is unclear whether there is any consensus among experts in clinical practice. We evaluated current expert opinion regarding the diagnosis and treatment of pancreatic duct disruption and disconnection in an international case vignette study. Methods: An online case vignette survey was sent to 110 international expert pancreatologists. Expert selection was based on publications in the last 5 years and/or participation in development of IAP/APA and ESGE guidelines on acute pancreatitis. Consensus was defined as agreement by at least 75% of the experts. Results: The response rate was 51% (n = 56). Forty-four experts (79%) obtained a MRI/MRCP and 52 experts (93%) measured amylase levels in percutaneous drain fluid to evaluate pancreatic duct integrity. The majority of experts favored endoscopic transluminal drainage for infected (peri)pancreatic necrosis and pancreatic duct disruption (84%, n = 45) or disconnection (88%, n = 43). Consensus was lacking regarding the treatment of patients with persistent percutaneous drain production, and with persistent sterile necrosis. Conclusion: This international survey of experts demonstrates that there are many areas for which no consensus existed, providing clear focus for future investigation

A study on the activation peptide released from procarboxypeptidase B (CAPAP) and anionic trypsinogen in patients with acute abdominal disorders of non-pancreatic origin

Background: The activation peptide released from procarboxypeptidase B, CAPAP, is a marker of the activation of pancreatic enzymes in acute pancreatitis while anionic trypsinogen (AT) levels in urine relate to leakage of unactivated proenzymes. Data on these markers in patients suffering from severe acute abdominal disorders of nonpancreatic origin are lacking. Purpose: To examine levels of CAPAP and AT in serum and urine from patients with severe acute abdominal disorders of non-pancreatic origin in order to better define the diagnostic specificity of these two markers in severe acute pancreatitis in relation to other acute intra-abdominal disorders. Subjects and Methods: The study included 54 patients with severe acute abdominal disorders of non-pancreatic origin with an APACHE II score >3. Immunoreactive CAPAP (irCAPAP) and immunoreactive AT (irAT) were measured in serum and urine using specific immunoassays. Results: In urine, irCAPAP levels were mildly increased (>2 nmol/l) in 13% of the patients with severe acute abdominal diseases of non-pancreatic origin, but on no occasion did the increase approach the cutoff levels described for severe acute pancreatitis (>100 nmol/l). However, irAT levels in serum and urine were increased (>50 mug/l) in 54% of the cases. Conclusion: Contrary to what is found for irAT, patients with acute abdominal pain of non-pancreatic origin rarely have markedly increased levels of irCAPAP in serum and urine. Copyright (C) 2003 S. Karger AG, Basel and IAP

Serum levels of procarboxypeptidase B and its activation peptide in patients with acute pancreatitis and non-pancreatic diseases

Background: Carboxypeptidase B from the pancreatic gland may exist in three different molecular and immunoreactive forms: the proenzyme, the active enzyme, and the activation peptide. Aims: To investigate levels of procarboxypeptidase B (proCAPB) and its activation peptide in serum in acute pancreatitis to test the accuracy of these two variables as markers for the diagnosis of acute pancreatitis and for prediction of pancreatic necrosis. To elucidate whether leakage of proenzymes and activation of proenzymes reflect two different pathophysiological events in acute pancreatitis. Methods: Sera from patients with acute pancreatitis (n=85) and acute abdominal pain of non-pancreatic origin (n=53) were analysed for proCAPB and its activation peptide. Patients with pancreatitis were divided into necrotising (n=33) and oedematous attacks (n=52) using contrast enhanced computed tomography. Accuracy was determined using receiver operating characteristic curve analysis. Results: Immunoreactive carboxypeptidase B activation peptide (ir-CAPAP) concentration in serum on admission was 0.7 nmol/l (0-18.1) in patients with oedematous pancreatitis compared with 5.8 nmol/l (1.9-34) in patients with later development of pancreatic necrosis. Elevated levels of the activation peptide on admission correlated with an accuracy of 92% to later development of pancreatic necrosis. Ir-proCAPB concentration in serum on admission was 16.0 nmol/l (1.4-50.5) in all patients with acute pancreatitis versus 0.3 nmol/l (0-3.6) in patients with non-pancreatic acute abdominal disorders. Cases with oedematous pancreatitis had ir-proCAPB levels of 15.4 nmol/l (1.4-50.5) versus 19.1 nmol/l (2.7-36.1) in cases with later development of pancreatic necrosis. Measurement of the proenzyme can thus be useful for the diagnosis of acute pancreatitis (accuracy 99%) but levels did not correlate with later development of pancreatic necrosis (accuracy 56%). Conclusion: Leakage of proenzymes occurs in acute pancreatitis, irrespective of severity, while development of pancreatic necrosis occurs only when there is activation of the proenzymes

Dexamethasone affects inflammation but not trypsinogen activation in experimental acute pancreatitis

Background/Aims: Trypsinogen activation and inflammation are early events in acute pancreatitis. This experimental study aimed to show the effects of dexamethasone on them. Methods: Cerulein and taurocholate pancreatitis were induced in 2 groups of 12 Wistar rats each. Six animals per group were injected with dexamethasone 1 h prior to the induction of acute pancreatitis. Amylase, phospholipase A2, TNF-alpha, IL-6, IL-10, alpha 2-antiplasmin in plasma and trypsinogen activation peptide (TAP) in urine were measured in healthy rats, then 0.5 and 6 h after pancreatitis induction. A severity score based on edema, necrosis and ascites was calculated at 6 h. TNF-alpha, IL-6 and IL-10 were measured 0.5 h after laparotomy in a control sham-operated group of 6 rats. Results: Inflammatory markers increased early in the course of both mild and severe acute pancreatitis and were significantly lowered by dexamethasone. The severity score was higher in taurocholate than in cerulein pancreatitis. It was significantly decreased by dexamethasone only in rats with mild pancreatitis. TAP remained unchanged in mild pancreatitis compared to healthy animals but increased late in the course of taurocholate pancreatitis. Trypsinogen activation was not affected by dexamethasone at all. Conclusion: Inflammation occurred earlier than the increase in urinary TAP in severe pancreatitis in rats. Dexamethasone inhibited inflammation but had no influence on TAP levels in experimental mild and severe acute pancreatitis. Copyright (C) 2008 S. Karger AG, Basel